Androgen insensitivity syndrome: a review

Batista, Rafael Loch; Costa, Elaine Maria Frade; Rodrigues, Andresa De Santi; Gomes, Nathália Lisboa; Faria, José Antônio Diniz; Nishi, Mirian Yumie; Arnhold, Ivo Jorge Prado; Domenice, Sorahia; Mendonca, Berenice B.

doi:10.20945/2359-3997000000031

Cited by 107 publications

(85 citation statements)

References 63 publications

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“…There may also be a slight loss of function of AR contributing to SBMA pathogenesis (Thomas et al, 2006). However, motor impairment has not been observed in AR knockout mice (Yeh et al, 2002) or in severe testicular feminisation patients lacking AR function (Batista et al, 2018). Interestingly, recent reports have shown that muscle may play a more prominent part in disease than previously thought and indeed may be a key site of AR toxicity and the development of pathology in SBMA (Cortes et al, 2014a;Lieberman et al, 2014;Milioto et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice

Gray

Annan

Dick

et al. 2020

Disease Models &Amp; Mechanisms

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Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's Disease, is a late-onset, X-linked, progressive neuromuscular disease, which predominantly affects males. The pathological hallmarks of the disease are defined by selective loss of spinal and bulbar motor neurons, accompanied by weakness, atrophy and fasciculations of bulbar and limb muscles. SBMA is caused by a CAG repeat expansion in the gene that encodes the androgen receptor (AR) protein. Disease manifestation is androgen dependent and results principally from a toxic gain of AR function. There are currently no effective treatments for this debilitating disease. It is important to understand the course of the disease in order to target therapeutics to key pathological stages. This is especially relevant in disorders such as SBMA, where disease can be identified prior to symptom onset, through family history and genetic testing. To fully characterise the role of muscle in SBMA, we undertook a longitudinal physiological and histological characterisation of disease progression in the AR100 mouse model of SBMA. Our results show that the disease first manifests in skeletal muscle, prior to any motor neuron degeneration, which only occurs in late stage disease. These findings reveal alterations in muscle function, including reduced muscle force and changes in contractile characteristics, are early pathological events in SBMA mice and suggest that muscle-targeted therapeutics may be effective in SBMA.

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Section: Introductionmentioning

confidence: 99%

Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice

Gray

Annan

Dick

et al. 2020

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Several different mutations of the AR gene have been identified so far. Some of them might lower its function leading to the androgen insensitivity syndrome [33]; they encompass pathologic conditions which occur with different clinical phenotypes: spinal and bulbar muscular atrophy and partial or complete androgen resistance (i.e., Morris syndrome). Conversely, some other mutations of AR can be activating as it does in prostate cancer.…”

Section: Androgen Receptor: Structure and Functionmentioning

confidence: 99%

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Giagulli

Silvestrini

Bruno

et al. 2020

International Journal of Endocrinology

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Hypogonadotropic hypogonadism (HH) can be sustained by organic or functional alterations of the hypothalamic-pituitary-testicular axis. Functional HH is related to systemic alterations, such as obesity or chronic inflammatory diseases, but could contribute to a negative course of the illness. For such situation, according to results obtained in infertile women, the administration of selective estrogen receptor modulators (SERMs) has been proposed in males too, with positive results on both metabolic and sexual function. This class of medications increases gonadotropin levels via antagonism to the estrogenic receptor; similar biological effects are also exerted by aromatase inhibitors (AIs), despite different mechanism of action. After a brief review of trials regarding SERMs and AIs use in male HH, we describe the structure and function of the androgen receptor (AR) as a basis for clinical research about compounds able to bind to AR, in order to obtain specific effects (SARMs). The tissue selectivity and different metabolic fate in comparison to testosterone can potentiate anabolic versus androgenic effects; therefore, they might be a valid alternative to testosterone replacement therapy avoiding the negative effects of testosterone (i.e., on prostate, liver, and hematopoiesis). Trials are still at an early phase of investigation and, at the moment, the application seems to be more useful for chronic disease with catabolic status while the validation as replacement for hypogonadism requires further studies.

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“…Complete Androgen Insensitivity in Girls with Inguinal Hernias: A Serendipity Opportunity for Early Diagnosis Rafael Loch Batista 1,2 1 Hospital das Cl ınicas da Universidade de São Paulo, Endocrinology Unit, Laborat orio de Investigações M edicas LIM/42, HCFMUSP, São Paulo/SP, Brazil; 2 Instituto de Psiquiatria HCFMUSP, São Paulo/SP, Brazil…”

Section: Commentarymentioning

confidence: 99%

“…Collectively, these conditions are named 46,XY differences of sexual development (DSD). Androgen insensitivity syndrome (AIS) is the most common cause of DSD in individuals with 46,XY karyotype [2]. At molecular level, it is caused by allelic variants in the AR gene, which is located at X chromosome, conferring a X-linked pattern of inheritance.…”

Section: Commentarymentioning

confidence: 99%

Androgen insensitivity syndrome: a review

Cited by 107 publications

References 63 publications

Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice

Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Complete Androgen Insensitivity in Girls with Inguinal Hernias: A Serendipity Opportunity for Early Diagnosis

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